A raised CRP in a client with depression
- In 11 randomized trials analysed at C-reactive protein (CRP) of 2 mg/L or higher, anti-inflammatory drugs reduced depressive symptom severity more than placebo: Hedges' g = 0.35, 95% CI 0.05 to 0.64, n = 321.
- Four of those trials measured anhedonia (n = 163). The drugs reduced it more than placebo: Hedges' g = 0.40, 95% CI 0.08 to 0.71.
- Treatment response was 49% on drug and 41% on placebo (8 trials, RR 1.28, 95% CI 0.997 to 1.64). Remission was 23% and 21% (7 trials, RR 1.18, 95% CI 0.71 to 1.95). The authors report neither difference as statistically significant.
- The review covered 19 placebo-controlled trials, 14 of them pooled, lasting from 2 to 12 weeks. The CRP analyses come from 11 of the 14, and the authors note that some results are post hoc analyses.
Sooner or later a client mentions that a doctor asked about C-reactive protein, or that a blood panel showed it raised. A meta-analysis in the American Journal of Psychiatry gives that remark a clinical meaning: among depressed adults with CRP of 2 mg/L or higher, anti-inflammatory drugs lowered symptoms more than placebo did.
Eleven trials, six drug groups
The authors found 19 placebo-controlled trials of anti-inflammatory drugs in depression and pooled 14. The drugs were minocycline (5 trials), NSAIDs (5), TNF inhibitors (4), interleukin-6 inhibitors (2), MAPK inhibitors (2) and recombinant interleukin-2 (1). Treatment lasted from two to 12 weeks, and in 13 trials the drug was added to existing treatment.
Eleven trials could be analysed at CRP of 2 mg/L or higher. Depressive symptom severity fell more on drug than on placebo (Hedges' g = 0.35, 95% CI 0.05 to 0.64, n = 321). Four of those trials measured anhedonia (g = 0.40, 95% CI 0.08 to 0.71, n = 163). Response was 49% versus 41% and remission 23% versus 21%; the authors do not call either difference significant.
Talking about CRP with a client and with the prescriber
The drug decision belongs to the physician. What changes is the conversation around it. A client who hears "your inflammation is raised" may take it as proof that the depression is purely bodily, or that therapy was beside the point. Neither follows from these numbers: scores moved by about a third of a standard deviation, and response and remission did not differ significantly from placebo.
So treat CRP as a variable, not a verdict. If a client mentions a raised value, ask who ordered it and whether the prescriber knows the full depression history, including how long anhedonia has been present. With consent, pass that history on. Do not promise that an anti-inflammatory will lift the mood, and keep your own work going alongside the physician's.
An elevated CRP is a variable to bring to the client's physician, not a reason to promise that a drug will lift the mood.
The authors state that confidence intervals are broad and individual trials small, particularly for anhedonia, so replication in larger trials is needed. Seven of the 19 trials were rated at high risk of bias, a common reason being that trials did not recruit on inflammation or reported post hoc analyses. Few trials assessed anhedonia with validated measures, and drugs, doses and trial length varied widely.